Overview

Although uncommon, carcinoma of the gallbladder (GB) is the most common primary hepatobiliary carcinoma, is the fifth most common malignancy of the gastrointestinal (GI) tract, and predominantly affects older persons with long-standing cholecystolithiasis. GB epithelial tumors tend to behave similarly to other GI adenocarcinomas. When the diagnosis is made incidentally at the time of cholecystectomy, surgical resection can be curative
[1, 2, 3] ; however, more commonly, the tumor is unresectable and rarely diagnosed preoperatively despite patients' symptoms. Early diagnosis can improve the clinical outcome and cure rate of GB carcinoma.

The following are images of gallbladder carcinoma from 2 imaging modalities.

Sagittal sonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was primary papillary adenocarcinoma of the gallbladder.

Preferred examination

Ultrasonography (US), which is readily available, noninvasive, and cost-effective, is the imaging modality of choice for GB carcinoma.
[4, 5, 6] However, US cannot stage the tumor. The visualization of lymph nodes, intraperitoneal disease, and distant metastases is difficult.

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Radiography

Plain abdominal radiographic films have a limited role in GB carcinoma. The images may demonstrate porcelain GB, calcified gallstones, and, rarely, biliary gas from GB-enteric fistula. Mucinous tumors may produce vague or punctate calcification in the primary tumor or in metastatic foci that may be visible on plain films. Barium studies, if positive, show duodenal invasion and displacement. Transverse colon invasion may occasionally be seen.

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Computed Tomography

Computed tomography (CT) scanning can detect GB masses and thickening of the GB wall, as well as the extent of hepatic invasion (see the following 2 images).
[7, 8] Peritoneal or distant disease, although uncommon, can be seen.

Computed tomography scan in a 65-year-old man. This image depicts squamous cell carcinoma of the gallbladder and invasion of the liver.

Computed tomography (CT) scan in a 65-year-old man with squamous cell carcinoma of the gallbladder and invasion of the liver (same patient as in the previous image). This CT scan depicts a lower cut through the liver than does the previous image.

Three patterns of findings are identified on CT scans. In 50% of patients, a heterogeneous mass that replaces the GB is present. The term "jam-packed GB" refers to filling of the entire GB lumen by tumor.

Focal or diffuse wall thickening is seen on CT scans in approximately 25% of patients, but this finding is often better appreciated on US. The thickened GB wall may show abnormally bright or persistent enhancement on infused CT scans.

In the remaining 20-25% of patients, a discrete intraluminal mass that enhances heterogeneously is visualized after the administration of intravenous contrast. Trapped stones within the mass may occasionally be seen. CT scans may also show biliary dilatation and metastases.

False positives/negatives

Xanthogranulomatous cholecystitis is an inflammatory process that cannot be reliably distinguished from GB carcinoma on CT scans because of multiple, overlapping features, such as GB wall thickening and involvement of the surrounding tissues, including portal lymph node, fat, and liver tissue.

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Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is not commonly used in the diagnostic process for GB carcinoma. The findings are analogous to those from CT scanning. The tumor is usually bright on T2-weighted images and is poorly marginated. On T1-weighted images, relative to the liver, the GB carcinoma ranges from isointense to hypointense.
[4]

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Ultrasonography

US is the most commonly used imaging modality for evaluating GB carcinoma; however, there have been no identified pathognomonic findings.
[9] Indirect signs that suggest the presence of GB carcinoma are as follows:

GB wall thickening

Single or multiple intraluminal mass

Extraluminal mass that extends to the liver

Polyps larger than 1 cm in diameter

The thickening associated with early lesions is rarely detected. More advanced lesions may produce marked mural thickening with irregular and mixed echogenicity, as shown in the first image below; this is the second most common manifestation of GB carcinoma, accounting for 20-30% of patients. The GB may be small, normal, or distended, and gallstones are often present (see the second image below). GB wall thickening is nonspecific and may be seen in multiple medical conditions, including acute and chronic cholecystitis, heart failure, hypoalbuminemia, hepatitis, and cirrhosis. However, the GB wall thickening in these patients is usually diffuse in contrast to the focal thickening in patients who have GB carcinoma.

Sagittal sonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was primary papillary adenocarcinoma of the gallbladder.

The polyps or mass are of homogeneous echotexture without evidence of shadowing. The polyps are usually sessile and only rarely have a stalk; this is the least common manifestation of GB carcinoma, accounting for 15-25% of patients. Visualization of a polyp that is smaller than 1 cm in the appropriate age group should arouse suspicion for adenoma/adenocarcinoma, because only these incidental early lesions have a good prognosis. Gallstones may also be present and may prevent recognition of a small polypoid mass. Tumefactive sludge can mimic a mass.

An extraluminal mass is often accompanied by a large mass that replaces the GB fossa. The mass is often complex, with visible areas of necrosis; this is the most common manifestation of GB carcinoma, accounting for 40-65% of GB carcinomas (see the second image above). According to studies, polyps with a diameter of more than 1 cm are malignant in 23-88% of patients.

A mass that arises from the GB may be difficult to differentiate from a mass that arises from the liver. The visualization of gallstones located centrally in a solid mass can help make the diagnosis. Adenomyomatosis can also cause focal GB wall thickening. This benign condition may mimic a GB tumor. US may demonstrate focal or diffuse wall thickening, with echogenic foci in Rokitansky-Aschoff sinuses that are often seen as "comet-tail" reverberation artifacts.

Benign polypoid lesions are difficult to distinguish from polypoid carcinoma; the cauliflower-like appearance suggests malignancy. Polyps smaller than 5 mm are unlikely to be malignant; polypoid lesions that are 5-10 mm in size should be followed up. In a patient with melanoma, metastases can cause multiple polypoid lesions. Tumefactive sludge can also mimic an intraluminal mass; usually, this is easy to differentiate by demonstrating the mobility of the sludge. Color Doppler US can also be used; the presence of flow within the lesion indicates that it is a solid mass rather than sludge.

High-resolution ultrasound (HRUS) has been shown to enable accurate T categorization of gallbladder carcinoma and to provide high-resolution images of gallbladder polyps. HRUS may also have a role in stratifying the risk for malignancy.
[10] Another study found that contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) may improve the preoperative diagnostic accuracy and interobserver agreement in the differential diagnosis of gallbladder wall thickening.
[11]

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Nuclear Imaging

Nonopacification of the GB on cholescintigraphy with technetium-99m (99m Tc) iminodiacetic acid analogue scanning is a nonspecific sign that indicates the possibility of carcinoma. This modality is not commonly used, having generally been replaced by US.

(18)F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-CT has been used to determine management of biliary tumors.
[12]

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Angiography

Angiography may demonstrate the neovascularity that arises from the cystic arteries, as well as arterial and venous encasement in the area of the GB, although this modality is not used as a diagnostic tool.

Sagittal sonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was primary papillary adenocarcinoma of the gallbladder.

Transverse ultrasonogram in a 66-year-old man. This image shows the gallbladder is filled with shadowing stones (arrow) that are surrounded by the hypoechoic liver parenchyma, which represents direct invasion by carcinoma. The diagnosis was squamous cell carcinoma of the gallbladder.

Computed tomography scan in a 65-year-old man. This image depicts squamous cell carcinoma of the gallbladder and invasion of the liver.

Computed tomography (CT) scan in a 65-year-old man with squamous cell carcinoma of the gallbladder and invasion of the liver (same patient as in the previous image). This CT scan depicts a lower cut through the liver than does the previous image.

Abraham H Dachman, MD, FACR Professor, Department of Radiology, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine; Director of CT, Department of Radiology, The University of Chicago Hospitals